Areca, a type of palm tree also known as Areca catechu , is generally cultivated in India, Southeast Asia, the East Indies and East Africa. The fruit of the Areca tree is a nut containing a single seed having a thin seed coat. The nut of the Areca catechu tree contains several pyridine-derived alkaloids, including arecoline, Arecaidine, guvacoline and guvacine which may be as high as 1.7% of the nut's make-up. In nature, the highest single alkaloid component concentration in Areca nut is the arecoline, a methyl ester. (1)
The Areca nut is known around the world for its stimulating effects, and it is chewed by millions of people who seek the stimulating properties of the nut. Betel quid is the combination of Areca catechu nut and piper betel leaf, and other components, and is the most common use of the Areca plant. There are approximately 600 million betel quid chewers in the world. Betel quid chewing is a major etiologic factor of oral cancer. It has been found that Areca nut and arecoline inhibit the growth of oral mucosal fibroblasts and keratinocytes. The effects of long-term use include oral submucosus fibrosis, leukoplakia and oral cancer. Studies have shown that Areca nut extract induces DNA breaks and unscheduled DNA synthesis and differentiation of oral keratinocytes. Arecoline also displays genotoxic effects.
The autonomic effects of Areca on the user include sweating and facial flush; skin temperature rises and heart rate also increases while chewing Areca. Specifically, the alkaloids arecoline and Arecaidine, although initially causing a brief depressor response, subsequently produce an increase in arterial blood pressure and heart rate. These stimuli are mediated through muscarinic M1 receptors.
In animals, arecoline, Arecaidine, guvacoline and guvacine are known to possess activity as agonists at muscarinic acetylcholine receptors. Additionally, arecoline has been shown to have indirect effects on catecholamine levels, while Arecaidine and guvacine inhibit gamma-aminobutyric acid (GABA) receptor uptake in micromolar concentrations.
The chewing of betel quid has led to increased levels of oral cancers. For example, in the United Kingdom, with its large population of Southeastern Asians, many of whom routinely chew betel quid, there are over 3800 new cases of oral cancer and 1700 deaths each year. One combination of betel quid uses the betel pepper leaf as a wrapper for various fillings that include Areca palm nut, as pastes, crushed fragments or shavings, along with tobacco, saffron, slaked lime, and aromatic spices and seeds. Some of these combinations add to the carcinogenicity of betel quid. The presence of arecoline, which is the major alkaloid compound in the Areca nut, has been linked to precancerous conditions, including oral mucosal fibrosis.
What is needed are compositions that provide the desired physiological effects provided by Areca catechu nut and that have lowered carcinogens, particularly arecoline. What is also needed are methods of altering the alkaloid profile of extracts of the Areca nut to provide compositions having alkaloid profiles that are different from the native plant material.